scholarly journals Adipose Stem Cells from Type 2 Diabetic Mice Exhibit Therapeutic Potential in Wound Healing

2020 ◽  
Author(s):  
Yongfa Sun ◽  
Lili Song ◽  
Yong Zhang ◽  
Hongjun Wang ◽  
Xiao Dong
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Therapeutic Potential ◽  
Diabetic Patients ◽  
Therapeutic Effects ◽  
Skin Damage ◽  
Impaired Wound Healing ◽  
Collagen Iii

Abstract BACKGROUND: Diabetic patients suffer from impaired wound healing. Mesenchymal stem cell (MSC) therapy represents a promising approach toward improving skin wound healing through release of soluble growth factors and cytokines that stimulate new vessel formation and modulate inflammation. Whether adipose-derived MSCs (ASCs) from type 2 diabetes donors are suitable for skin damage repair remains largely unknown. METHODS: In this study, we compared the phenotype and functionality of ASCs harvested from high fat diet (HFD) and streptozotocin (STZ)-induced T2D or control mice, and assessed their abilities to promote wound healing in an excisional wound splinting mouse model with T2D. RESULTS: T2D ASCs expressed similar cellular markers as control ASCs, but secreted less hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), and transforming growth factor β (TGF-β). T2D ASCs were somewhat less effective in promoting healing of the wound, as manifested by slightly reduced re-epithelialization, cutaneous appendage regeneration, and collagen III deposition in wound tissues. In vitro, T2D ASCs promoted proliferation and migration of skin fibroblasts to a comparable extent as control ASCs via suppression of inflammation and macrophage infiltration. CONCLUSIONS: From these findings, we conclude that, although ASCs from T2D mice are marginally inferior to control ASCs, they possess comparable therapeutic effects in wound healing.

scholarly journals Adipose Stem Cells from Type 2 Diabetic Mice Exhibit Therapeutic Potential in Wound Healing

2020 ◽  
Author(s):  
Yongfa Sun ◽  
Lili Song ◽  
Yong Zhang ◽  
Hongjun Wang ◽  
Xiao Dong
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Therapeutic Potential ◽  
Diabetic Patients ◽  
Therapeutic Effects ◽  
Skin Damage ◽  
Impaired Wound Healing ◽  
Collagen Iii

Abstract BACKGROUND: Diabetic patients suffer from impaired wound healing. Mesenchymal stem cell (MSC) therapy represents a promising approach toward improving skin wound healing through release of soluble growth factors and cytokines that stimulate new vessel formation and modulate inflammation. Whether adipose-derived MSCs (ASCs) from type 2 diabetes donors are suitable for skin damage repair remains largely unknown. METHODS: In this study, we compared the phenotype and functionality of ASCs harvested from high fat diet (HFD) and streptozotocin (STZ)-induced T2D or control mice, and assessed their abilities to promote wound healing in an excisional wound splinting mouse model with T2D. RESULTS: T2D ASCs expressed similar cellular markers as control ASCs, but secreted less hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), and transforming growth factor β (TGF-β). T2D ASCs were somewhat less effective in promoting healing of the wound, as manifested by slightly reduced re-epithelialization, cutaneous appendage regeneration, and collagen III deposition in wound tissues. In vitro, T2D ASCs promoted proliferation and migration of skin fibroblasts to a comparable extent as control ASCs via suppression of inflammation and macrophage infiltration. CONCLUSIONS: From these findings, we conclude that, although ASCs from T2D mice are marginally inferior to control ASCs, they possess comparable therapeutic effects in wound healing.

scholarly journals Increased Growth Factors Play a Role in Wound Healing Promoted by Noninvasive Oxygen-Ozone Therapy in Diabetic Patients with Foot Ulcers

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Jing Zhang ◽  
Meiping Guan ◽  
Cuihua Xie ◽  
Xiangrong Luo ◽  
Qian Zhang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Standard Therapy ◽  
Transforming Growth Factor ◽  
Ozone Treatment ◽  
Foot Ulcers ◽  
Control Group ◽  
Diabetic Patients ◽  
Therapeutic Effects ◽  
Ozone Therapy

Management of diabetic foot ulcers (DFUs) is a great challenge for clinicians. Although the oxygen-ozone treatment improves the diabetic outcome, there are few clinical trials to verify the efficacy and illuminate the underlying mechanisms of oxygen-ozone treatment on DFUs. In the present study, a total of 50 type 2 diabetic patients complicated with DFUs, Wagner stage 2~4, were randomized into control group treated by standard therapy only and ozone group treated by standard therapy plus oxygen-ozone treatment. The therapeutic effects were graded into 4 levels from grade 0 (no change) to grade 3 (wound healing). The wound sizes were measured at baseline and day 20, respectively. Tissue biopsies were performed at baseline and day 11. The expressions of vascular endothelial growth factor (VEGF), transforming growth factor-β(TGF-β), and platelet-derived growth factor (PDGF) proteins in the pathologic specimens were determined by immunohistochemical examinations. The effective rate of ozone group was significantly higher than that of control group (92% versus 64%,P<0.05). The wound size reduction was significantly more in ozone group than in control group (P<0.001). After treatment, the expressions of VEGF, TGF-β, and PDGF proteins at day 11 were significantly higher in ozone group than in control group. Ozone therapy promotes the wound healing of DFUs via potential induction of VEGF, TGF-β, and PDGF at early stage of the treatment. (Clinical trial registry number isChiCTR-TRC-14004415).

Transforming growth factor beta 1 dependent regulation of Tenascin-C in radiation impaired wound healing

2004 ◽  
Vol 72 (3) ◽  
pp. 297-303 ◽  
Author(s):  
Falk Wehrhan ◽  
Franz Rödel ◽  
Gerhard G. Grabenbauer ◽  
Kerstin Amann ◽  
Wolfgang Brückl ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Impaired Wound Healing ◽  
Tenascin C ◽  
Growth Factor Beta

Angiogenic Growth Factors: Their Effects and Potential in Soft Tissue Wound Healing

1992 ◽  
Vol 101 (4) ◽  
pp. 349-354 ◽  
Author(s):  
David B. Hom ◽  
Robert H. Maisel
Keyword(s):  
Wound Healing ◽  
Growth Factors ◽  
Growth Factor ◽  
Soft Tissue ◽  
Transforming Growth Factor Beta ◽  
Animal Studies ◽  
Transforming Growth Factor ◽  
Therapeutic Potential ◽  
Angiogenic Growth Factors

Since their discovery 30 years ago, angiogenic growth factors have been demonstrated to stimulate neovascularization in vitro and in animal studies. Over the last decade, knowledge gained in the field of angiogenic growth factors has grown immensely. These angiogenic growth factors exist in four major families: fibroblast growth factor (FGF), transforming growth factor beta (TGF-β), platelet-derived growth factor (PDGF), and epidermal growth factor (EGF). Each has the ability to induce soft tissue vascularization in microgram quantities. In animal models, FGF, TGF-β, PDGF, and EGF have been shown to enhance soft tissue wound healing. In human clinical trials, EGF and a mixture of PDGFs have been demonstrated to accelerate epidermal regeneration in cutaneous wounds. These factors have considerable therapeutic potential in the areas of soft tissue wound healing and otolaryngology. This article reviews important aspects of angiogenic growth factors and discusses their future potential in soft tissue wound healing.

Methylglyoxal administration induces diabetes-like microvascular changes and perturbs the healing process of cutaneous wounds

2005 ◽  
Vol 109 (1) ◽  
pp. 83-95 ◽  
Author(s):  
Jorge BERLANGA ◽  
Danay CIBRIAN ◽  
Isabel GUILLÉN ◽  
Freya FREYRE ◽  
José S. ALBA ◽  
...  
Keyword(s):  
Wound Healing ◽  
Endothelial Cells ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Prolonged Exposure ◽  
Healing Process ◽  
Vascular Complications ◽  
Tissue Growth ◽  
Protein Glycation ◽  
Impaired Wound Healing

Increased formation of MG (methylglyoxal) and related protein glycation in diabetes has been linked to the development of diabetic vascular complications. Diabetes is also associated with impaired wound healing. In the present study, we investigated if prolonged exposure of rats to MG (50–75 mg/kg of body weight) induced impairment of wound healing and diabetes-like vascular damage. MG treatment arrested growth, increased serum creatinine, induced hypercholesterolaemia (all P<0.05) and impaired vasodilation (P<0.01) compared with saline controls. Degenerative changes in cutaneous microvessels with loss of endothelial cells, basement membrane thickening and luminal occlusion were also detected. Acute granulation appeared immature (P<0.01) and was associated with an impaired infiltration of regenerative cells with reduced proliferative rates (P<0.01). Immunohistochemical staining indicated the presence of AGEs (advanced glycation end-products) in vascular structures, cutaneous tissue and peripheral nerve fibres. Expression of RAGE (receptor for AGEs) appeared to be increased in the cutaneous vasculature. There were also pro-inflammatory and profibrotic responses, including increased IL-1β (interleukin-1β) expression in intact epidermis, TNF-α (tumour necrosis factor-α) in regions of angiogenesis, CTGF (connective tissue growth factor) in medial layers of arteries, and TGF-β (transforming growth factor-β) in glomerular tufts, tubular epithelial cells and interstitial endothelial cells. We conclude that exposure to increased MG in vivo is associated with the onset of microvascular damage and other diabetes-like complications within a normoglycaemic context.

scholarly journals Regulation of the expression of stromelysin-2 by growth factors in keratinocytes: implications for normal and impaired wound healing

1996 ◽  
Vol 320 (2) ◽  
pp. 659-664 ◽  
Author(s):  
Marianne MADLENER ◽  
Cornelia MAUCH ◽  
Walter CONCA ◽  
Maria BRAUCHLE ◽  
William C. PARKS ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factors ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Keratinocyte Growth Factor ◽  
Healing Process ◽  
Branching Morphogenesis ◽  
Transforming Growth Factor Β1 ◽  
Impaired Wound Healing ◽  
Factor Α

Keratinocyte growth factor (KGF) has been implicated in wound re-epithelialization and branching morphogenesis of several organs. To determine whether KGF induces these effects via induction of matrix metalloproteinase expression we have analysed the effect of KGF on the expression of stromelysin-2 in cultured HaCaT keratinocytes. Here we show a strong induction of stromelysin-2 mRNA within 5–8 h of stimulation of these cells with KGF. The degree of induction was similar to that achieved by treatment with epidermal growth factor or tumour necrosis factor α, whereas the stimulatory effect of transforming growth factor β1 was even stronger. To determine whether the induction of stromelysin-2 expression by growth factors and cytokines might be important for wound healing, we analysed the expression of this gene during the healing process of full-thickness excisional wounds in mice. Whereas stromelysin-2 mRNA could hardly be detected in unwounded skin, a biphasic induction was seen after injury and highest levels were found at days 1 and 5 after wounding. Hybridization in situ revealed the presence of stromelysin-2 mRNA in basal keratinocytes at the wound edge but not in the underlying mesenchymal tissue. During impaired wound healing as seen in glucocorticoid-treated mice, stromelysin-2 expression was significantly increased compared with untreated control mice. Taken together, these results suggest that correct regulation of this broad-spectrum metalloproteinase might be important for normal repair.

scholarly journals Effect of Electrical Stimulation on Diabetic Human Skin Fibroblast Growth and the Secretion of Cytokines and Growth Factors Involved in Wound Healing

Biology ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 641
Author(s):  
Atieh Abedin-Do ◽  
Ze Zhang ◽  
Yvan Douville ◽  
Mireille Méthot ◽  
Mahmoud Rouabhia
Keyword(s):  
Wound Healing ◽  
Electrical Stimulation ◽  
Growth Factors ◽  
Growth Factor ◽  
Human Skin ◽  
Direct Current ◽  
Diabetic Patients ◽  
Fibroblast Growth ◽  
Impaired Wound Healing ◽  
Fibroblast Adhesion

Diabetic foot ulcers are indicative of an impaired wound healing process. This delay may be resolved through electrical stimulation (ES). The goal of the present study was to evaluate the effect of ES on diabetic fibroblast adhesion and growth, and the secretion of cytokines and growth factors. Diabetic human skin fibroblasts (DHSF) were exposed to various intensities of direct current ES (100, 80, 40 and 20 mV/mm). The effect of ES on fibroblast adhesion and growth was evaluated using Hoechst staining, MTT and trypan blue exclusion assays. The secretion of cytokine and growth factor was assessed by cytokine array and ELISA assay. The long-term effects of ES on DHSF shape and growth were determined by optical microscopy and cell count. We demonstrated that ES at 20 and 40 mV/mm promoted cell adhesion, viability and growth. ES also decreased the secretion of pro-inflammatory cytokines IL-6 and IL-8 yet promoted growth factor FGF7 secretion during 48 h post-ES. Finally, the beneficial effect of ES on fibroblast growth was maintained up to 5 days post-ES. Overall results suggest the possible use of low-intensity direct current ES to promote wound healing in diabetic patients.

scholarly journals Ceftriaxone and Melittin Synergistically Promote Wound Healing in Diabetic Rats

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1622
Author(s):  
Nabil A. Alhakamy ◽  
Giuseppe Caruso ◽  
Basma G. Eid ◽  
Usama A. Fahmy ◽  
Osama A. A. Ahmed ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Hydroxypropyl Methylcellulose ◽  
Ion Pairing ◽  
Diabetic Rats ◽  
Control Group ◽  
Diabetic Patients ◽  
Type I ◽  
Tgf Β1

High glucose levels in diabetic patients are implicated in delay wound healing that could lead to more serious clinical complications. The aim of the present work was to examine the formulation of ceftriaxone (CTX) and melittin (MEL) as nanoconjugate (nanocomplex)-loaded hydroxypropyl methylcellulose (HPMC) (1.5% w/v)-based hydrogel for healing of acute wounds in diabetic rats. The CTX–MEL nanoconjugate, formulated by ion-pairing at different molar ratio, was characterized for size and zeta potential and investigated by transmission electron microscopy. CTX–MEL nanoconjugate was prepared, and its preclinical efficacy evaluated in an in vivo model of acute wound. In particular, the potential ability of the innovative CTX–MEL formulation to modulate wound closure, oxidative status, inflammatory markers, and hydroxyproline was evaluated by ELISA, while the histopathological examination was obtained by using hematoxylin and eosin or Masson’s trichrome staining techniques. Quantitative real-time PCR (qRT-PCR) of the excised tissue to measure collagen, type I, alpha 1 (Col1A1) expression and immunohistochemical assessment of vascular endothelial growth factor A (VEGF-A) and transforming growth factor beta 1 (TGF-β1) were also carried out to shed some light on the mechanism of wound healing. Our results show that the CTX–MEL nanocomplex has enhanced ability to regenerate epithelium, also giving better keratinization, epidermal proliferation, and granulation tissue formation, compared to MEL, CTX, or positive control. The nanocomplex also significantly ameliorated the antioxidant status by decreasing malondialdehyde (MDA) and increasing superoxide dismutase (SOD) levels. The treatment of wounded skin with the CTX–MEL nanocomplex also showed a significant reduction in interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) pro-inflammatory cytokines combined with a substantial increase in hydroxyproline, VEFG-A, and TGF-β1 protein expression compared to individual components or negative control group. Additionally, the CTX–MEL nanocomplex showed a significant increase in mRNA expression levels of Col1A1 as compared to individual compounds. In conclusion, the ion-pairing nanocomplex of CTX–MEL represents a promising carrier that can be topically applied to improve wound healing.

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